Tissue monitoring system for intravascular infusion

ABSTRACT

An infusion system has a capability to monitor infusion complications such as extravasation, tissue necrosis, infiltration, phlebitis, and blood clots. The infusion system has at least partially transparent flexible film barrier dressing in a flexible membrane that incorporates a plurality of sensors capable of detecting tissue condition and a control unit capable of coupling to the film barrier dressing that monitors signals from the sensors. A device is capable of executing non-invasive physiological measurements to characterize physiologic information from cross-sectional surface and subcutaneous tissue to detect the presence or absence of tissue conditions such as infiltration or extravasation during intravascular infusion. In some examples, the device utilizes depth-selective methods to sense, detect, quantify, monitor, and generate an alert notification of tissue parameters.

RELATED PATENTS AND APPLICATIONS

[0001] This application is related to U.S. patent application Ser. No.60/351,094, filed on Jan. 25, 2002.

[0002] The disclosed system and operating method are related to subjectmatter disclosed in the following co-pending patent applications thatare incorporated by reference herein in their entirety:

[0003] 1. U.S. patent application Ser. No. xx/xxx,xxx entitled, “FilmBarrier Dressing for Intravascular Infusion Tissue Monitoring System”,<attorney docket no.: 1013.P002 US> naming Karen Jersey-Willuhn andManuchehr Soleimani as inventors and filed on even date herewith;

[0004] 2. U.S. patent application Ser. No. xx/xxx,xxx entitled“Conductivity Reconstruction Based on Inverse Finite ElementMeasurements in a Tissue Monitoring System”, <attorney docket no.:1013.P003 US> naming Karen Jersey-Willuhn and Manuchehr Soleimani asinventors and filed on even date herewith.

BACKGROUND OF THE INVENTION

[0005] 1. Field of the Invention

[0006] The invention relates generally to physiological monitoringdevices and, more particularly, to tissue monitoring devices and methodsfor detecting harmful conditions including conditions that occur duringintravascular infusion.

[0007] 2. Relevant Background

[0008] An infusion system is commonly used to infuse a fluid into apatient's vascular system. Intravenous (IV) therapy is sometimesnecessary for patient treatment and is generally considered a safeprocedure. IV therapy is administered to approximately 80% ofhospitalized patients in the United States. Some form of IV complicationdevelops in nearly a third of patients receiving IV therapy. Mostcomplications do not progress to more serious problems, but cases withfurther complications of IV failure are difficult to predict.

[0009] Several complications may arise from the infusion processincluding extravasation, tissue necrosis, infiltration, phlebitis,venous inflammation, and others. These complications can result inprolonged hospitalization, infections, patient discomfort, patientdisfigurement, nerve damage, and additional medical complications andexpense. Phlebitis is the largest cause of intravascular infusionmorbidity. Infiltration and extravasation follow only phlebitis as IVmorbidity causes.

[0010] When complications of infiltration, extravasation, phlebitis, orblood clots occur, the standard of care requires prompt removal of theIV to minimize further complications since continued pumping of infusateexacerbates the complications. Immediate detection of complications andtermination of infusion reduces the possibility and damage of furthercomplications. IV complications can cause failure to infuse a neededdrug or fluid and lead to inadequate or sub-optimal therapeutic druglevels and hypo-volemia. Fluids that would lead to patient recovery mayfail to reach the appropriate organs or tissue. Under life-threateningconditions or where infusion is life-sustaining, a patient's failure toreceive fluids can be lethal. IV failure compromises patient safety.

[0011] Infiltration is the inadvertent administration of solution intosurrounding tissue. Extravasation is the inadvertent administration of asolution that is capable of causing tissue necrosis when the materialescapes or is infused outside the desired vascular pathway.

[0012] Extravasation sometimes results when an injection fluid, forexample a contrast medium, is injected into a blood vessel.Extravasation is the accidental infusion of injection fluid into tissuesurrounding a blood vessel rather than into the intended blood vessel.Various causes of complications that may occur with intravenousinfusions include fragile vasculature, valve disease, inappropriateneedle placement, infusion needle dislodgement of the cannula or needledelivering the fluid, microdilation of veins due to infusate chemicalproperties causing the material to leak from the vein. dislodgement fromthe vessel due to patient movement, or infusion needle piercing throughthe vessel wall also due to patient movement. IV complication riskincreases for elderly persons, children, cancer patients, andimmuno-compromised patients.

[0013] Patients under therapy with vesicant drugs includingchemotherapy, infusion of highly osmotic solutions, or high acid or lowbase solutions have risk of tissue necrosis if fluids are infusedoutside the vascular pathway. Examples infused agents include totalparenteral nutrients, chemotherapeutic alkalating drugs, alkalinesolutions, vasopressors (for example, Total Parenteral Nutrition (TPN)),antibiotics, hypertonic acids, KCI, and others. Many routinely-usedantibiotics and medications are capable of causing extravasations andtissue necrosis. Antineoplastics can cause severe and widespread tissuenecrosis if extravasation occurs. Chemotherapeutic agents are highlytoxic IV drugs. Several drugs for emergency use have a well-documentedhigh incidence of tissue damage. For example, administration ofessential vasopressor drug dopamine in life-threatening orlife-sustaining situations has a documented incidence of 68% tissuenecrosis or extravasation at the IV infusion site. Caretakers cannotanticipate which complication will progress including necrosis tomuscle.

[0014] Complications that may occur can cause serious patient injury bytissue trauma and toxicity of injection fluid. For example someinjection fluids such as contrast media or chemotherapy drugs can betoxic to tissue if undiluted by blood flow. As a consequence,extravasation should be detected as early as possible and injectionimmediately discontinued upon detection.

[0015] In infiltration and extravasation, a condition occurs in whichinfused fluid enters extravascular tissue rather than the blood streamoccurring, for example, when an infusion needle is not fully inserted tothe interior of a blood vessel. Infiltrating fluid is infused intointerstitial spaces between tissue layers, preventing proper intravenousdrug administration and possibly resulting in toxic or caustic effectsof direct contact of infused fluids with body tissues.

[0016] Infiltration and extravasation complications are costly andcompromise patient outcome. Complications include pain and prolongeddiscomfort that may last for months, prolonged healing, ischemicnecrosis due to vasoconstriction, opportunistic infections andsepticemia, ulceration, cosmetic and physical disfigurement, and directcellular toxicity for antineoplastic agents. Other complications includeskin grafting, flaps, and surgical debridements, sometimes multiple.Further complications are compartment syndrome, arteriolar compression,vascular spasm, nerve damage (sometimes permanent), muscular necrosis,functional muscular changes, functional loss of extremities, amputation,reflex sympathetic dystrophy, and chronic pain syndrome.

[0017] Infiltration and extravasation can cause catheter-relatedbloodstream infection, including sepsis. An estimated 200,000 to 400,000incidences of catheter-related infections occur annually, resulting inapproximately 62,500 deaths, 3.5 million additional hospital days fortreatment, and adds about $3.5 billion to the annual healthcare cost.Estimates of individual costs vary. A catheter-related bloodstreaminfection may cost $6,000 to $10,000 per incidence, and increase thehospital stay by up to 22 days.

[0018] Additional costs can be incurred. Additional medications may needto be injected to dilute or neutralize the effect of toxic drugs oncetissue necrosis has begun to decrease the caustic reaction and reducetissue damage. Surgical removal of the necrotic tissue may be required.Caretaker time, and therefore costs, increase since the extremitiestypically need to be elevated to improve venous return, warm and coolpacks are applied, psychological comfort and pain medications given, andseverity of the complication is monitored. A septic infection may causea serious infection such as an infection in the heart.

[0019] Other conditions that result from improper supply of fluid to apatient in intravenous therapy include venous inflammation andphlebitis, swelling at the infusion site. Phlebitis complicationsinclude inflammation or thrombophlebitis that occurs with about 10% ofall infusions. If phlebitis continues as the duration of infusioncontinues, the duration of the complication also increases. Phlebitispredisposes a patient to local and systemic infection. Phlebitis oftenresults in a complication of infection resulting from use of intravenouslines. Underlying phlebitis increases the risk of infection by anestimated twenty times with estimated costs of IV infections between$4000 and $6000 per occurrence. When phlebitis is allowed to continue,the vein becomes hard, tortuous, tender, and painful for the patient.The painful condition can persist indefinitely, incapacitates thepatient, and may destroy the vein for future use. Early assessment ofcomplication and quick response can reduce or eliminate damage and savethe vein for future use.

[0020] Another possible complication is blood clotting. IV needles andcannulas can become occluded with blood clots. As an occlusionintensifies, mechanical failure of the infusion can occur. Prescribedtherapy cannot be administered if the catheter is occluded and multipleother complications can result, such as pulmonary embolism.Complications may progress, forming a thrombus and causingthrombophlebitis, or catheter-associated infections or bactermias.

[0021] Tissue necrosis may result when some of the infused materials arevesicant or other materials are infused outside the vascular pathway.

[0022] The current methods for detecting phlebitis, necrosis,infiltration or extravasation in a medical surgical patient undergoingtherapeutic infusion are visual inspection and notification of pain bythe patient. A caretaker visually inspects the intravascular insertionsite or affected body parts for swelling, tenderness, discoloration.Otherwise, the caretaker requests or receives notification of pain bythe patient but generally when tissue damage has begun.

[0023] Another problem that occurs with infusion is that the patientnormally does not eat so that vital electrolytes can be lacking, acondition that is exacerbated by the patient's illness. One criticalelectrolyte is potassium. Medical protocols exist to replace neededpotassium, but the level of replacement is difficult to determine. Lowor high levels of potassium can lead to cardiac irritability and othercomplications. Electrolyte levels are commonly determined byelectrochemistry testing, usually by blood draws, a painful procedurethat commonly involves time delays for analysis.

[0024] What are needed are safe, reliable devices and methods thatsupply information on patient status of the presence or absence of IVcomplications. What are further needed are devices and methods thatnotify a caretaker of the occurrence of infiltration, extravasation,phlebitis, blood clots, and electrolyte levels with sufficient quicknessto reduce or eliminate tissue damage, patient discomfort, and additionalcomplications and associated costs.

SUMMARY OF THE INVENTION

[0025] An infusion system has a capability to monitor infusioncomplications such as extravasation, tissue necrosis, infiltration,phlebitis, and venous inflammation.

[0026] An infusion system comprises an at least partially transparentflexible film barrier dressing in a flexible membrane that incorporatesa plurality of sensors capable of detecting tissue condition and acontrol unit capable of coupling to the film barrier dressing thatmonitors signals from the sensors.

[0027] A device is capable of executing non-invasive physiologicalmeasurements to characterize physiologic information fromcross-sectional surface and subcutaneous tissue in one, two, or threedimensions to detect the presence or absence of tissue conditions suchas infiltration or extravasation during intravascular infusion. In someembodiments, the device utilizes depth-selective methods to sense,detect, quantify, monitor, and generate an alert notification of tissueparameters.

[0028] In some examples, the device uses one or more sensingtechnologies through a sensor pathway. Suitable sensing technologiesinclude bio-impedance sensing and photonics, for example, that can becombined to obtain data points that are stored, compared to a presetthreshold or pattern, quantified and displayed to a visual displayscreen.

[0029] Some systems can include an auditory alert signal thatannunciates upon detection of infiltration and extravasation. The systemcan respond to detection by adjusting the infusion rate at the infusionpump to reduce additional complications. The notification system enablesmedical surveillance of patient tissue status during infusion to allow acaretaker to intervene early to reduce injury or damage to tissue.

[0030] In some embodiments, an infusion system includes a monitoringsystem, sensor system, security for an intravascular catheter, a barrierdressing, a wireless status and alert notification system and adjustmentof infusion pump rate. Other embodiments may include a portion of thecomponents or varying components.

[0031] The infusion system monitors tissue conditions for indications oftissue infiltration, extravasation, phlebitis, and similar afflictionsthat may result as a complication of intravascular infusion.

[0032] The infusion system can monitor patients in a hospital, homecare, or ambulatory care setting when a patient is receiving intravenoustherapy.

[0033] The infusion system monitors patient tissue non-invasivelyutilizing one or more sensing technologies. In one illustrative example,the infusion system includes bioimpedance sensing alone. A secondillustrative example includes bioimpedance and infrared sensingtechnology with the two type of information combined and compared topredetermined values for threshold and pattern analysis.

[0034] In an illustrative application, the infusion system is applied toa patient at the initiation of an infusion and remains in placecontinuously through the infusion process. In some embodiments, theinfusion system control unit assembles a condition report and posts thecondition report on a visual display. The display can notify a caregiverof the presence or absence of conditions indicating an infiltration orextravasation. The infusion system can generate an auditory alert signalthat indicates occurrence of the condition.

[0035] In accordance with another aspect of the infusion system,biosensors are included in the film barrier dressing that are capable ofperforming analytic chemistry measurements at the point of care toenable rapid correction of electrolyte abnormalities and improvedmedical care.

[0036] Various aspects of the illustrative infiltration detection systemmay be utilized individually or in combination and are useful toidentify an abnormal infusion as early as possible without generating anexcessive number of false alarms. Aspects include an at least partiallytransparent film barrier dressing, sensors combined into the dressing,parameter modeling using one or more sensing technologies, conditiondetection using pattern recognition, generation of an alarm signal orannunication, generation of signals to control operation of an infusionpump, and others. Early detection allows attending medical staff torectify problems before significant damage occurs due to infiltrationand before the patient has been deprived of a significant amount of theintravenous therapy.

BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The features of the described embodiments believed to be novelare specifically set forth in the appended claims. However, embodimentsof the invention relating to both structure and method of operation, maybest be understood by referring to the following description andaccompanying drawings.

[0038]FIG. 1 is a schematic pictorial diagram that illustrates aninfusion system with a capability to monitor tissue conditions.

[0039]FIG. 2 is a schematic pictorial diagram that illustrates anotherexample of an infusion system with a capability to monitor tissueconditions.

[0040]FIG. 3 is a pictorial diagram showing an example of a suitablefilm barrier dressing for usage with an infusion system.

[0041]FIG. 4 is a schematic pictorial diagram that illustrates top andcross-sectional views of an example of a suitable electrical impedancesensor for usage in an infusion monitoring device.

[0042]FIG. 5 is a schematic block diagram illustrating another exampleof an electrical signal sensor in the configuration of an electrodearray sensor.

[0043]FIGS. 6A and 6B are block diagrams illustrating an example of anadditional electrical signal sensing technology, an electric signaltomogram scanner.

[0044]FIG. 7 is a schematic pictorial diagram showing an example of asuitable temperature sensing device for usage in the infusion system.

[0045]FIG. 8 is a schematic pictorial diagram that depicts a suitableoptical sensor for usage with the infusion system.

[0046]FIG. 9 is a schematic block diagram illustrating an example of acontrol unit suitable for usage with the illustrative infusion system.

[0047]FIG. 10 depicts a schematic pictorial view of an example of acontrol unit that is configured to be attachable to a patient's arm, IVpole, or other patient's appendage.

[0048]FIG. 11 is a flow chart that depicts an example of a technique fordetecting a harmful tissue condition during an infusion.

[0049]FIG. 12 is a schematic circuit diagram showing an impedance modelof tissue that is useful for describing conductivity reconstruction intissue.

[0050]FIG. 13 is a schematic block diagram that illustrates aneight-electrode configuration for a tissue impedance measurement.

[0051]FIG. 14 is an Electrical Impedance Tomography (EIT) block diagram.

[0052]FIG. 15 is a schematic pictorial diagram showing a Finite ElementMethod (FEM) mesh.

[0053]FIG. 16 is a highly schematic pictorial diagram that depictssensitivity analysis using the Jacobian matrix.

[0054]FIG. 17 is a flow chart that illustrates an embodiment of areconstruction method for Electrical Impedance Tomography.

DESCRIPTION OF THE EMBODIMENT(S)

[0055] Referring to FIG. 1, a schematic pictorial diagram illustrates aninfusion system 100 with a capability to monitor tissue conditions. Theinfusion system 100 can be used to infuse a flowable material or fluidin the form of liquid, gas, or a combination into a patient. Theillustrative infusion system 100 includes an infusion device 110 thatdelivers the infusion fluid and a conduit 112 for conducting the flowingmaterial from the infusion device 110 to the patient. The conduit 112comprises a flexible tubing 114 that couples to the infusion device 110and a cannula 116, such as a needle or catheter, that is capable ofinserting into the patient's vascular system.

[0056] The infusion system 100 is a noninvasive system that can beapplied to the surface skin for monitoring in one or more dimensionsusing depth-selective cross sectional surface and subcutaneous tissueover time in a patient receiving an intravascular infusion to measureand characterize tissue conditions. The infusion system 100 can be usedto detect and notify an individual of the presence or absence ofphysiological conditions that may indicate tissue complications such astissue infiltration and extravasation during intravascular infusions.

[0057] The infusion system 100 also comprises a sensor dressing 118 withsensors 120 integrated into a film barrier dressing 122, a sensor signalpathway 126, and a control unit 124 that controls monitoring, analysis,and notification of tissue condition. The sensor signal pathway 126 canconnect between the film barrier dressing 122 and the control unit 124,carrying data and control signals. The sensor signal pathway 126 can beof any suitable technology including conductive wires, fiberopticchannels, wireless channels, and others.

[0058] The film barrier dressing 122 is a tissue-contacting section thatis capable of temporary affixation to surface tissue over one or moretissue sites, typically including an intravascular insertion site. Thefilm barrier dressing 122 protects the skin and tissue in the vicinityof the infusion against exposure to pathogens in the environment,reducing the possibility of infection, and secures the catheter toreduce or eliminate motion that may result in complications. The filmbarrier dressing 122 is transparent or includes a transparent or clearwindow to allow visual of the infusion site and forms a structuralsupport for the sensors 120. The film barrier dressing 122 has one ormore adhesive layers capable of contacting and affixing to patienttissue and also capable of securing a needle or intravenous catheteragainst the skin and sealing the top of an intravascular insertion.

[0059] In some embodiments, the film barrier dressing 122 is a tissuecontacting dressing that at least partially attaches to tissue andcontains a polymer adhesive suspended in a neutral protein compound. Theadhesive can be loosened or removed by applying water or alcohol.

[0060] The sensors 120 can be of a single type or multiple types and arecapable of detecting signals using one or more sensing technologies.Suitable sensor types include bio-impedance, spectrometry,spectrophotometer, oximeter, photonics, other optical technology,magnetoresistive, micro-electro-mechanical system (MEMS) sensors,acoustic sensors, and others.

[0061] In some examples, the sensors 120 contain one or more elementscapable of sending and receiving signals from tissue in one or more bodylocations. The sensors 120 comprise one or more sensor arrays adaptedfor transmitting signals into tissue and receiving signals from thetissue using one or more sensing technologies.

[0062] In one particular example, the sensors 120 acquire signals usingtwo sensor technologies including a bio-impedance sensor and an opticalsensor. Other embodiments may include only a single sensor, other typesof sensors, or more than two sensors. The bio-impedance sensor isconnected to the control unit 124 via an electrically-conductive sensorpathway and a spectrophotometry sensor is connected to the control unit124 using a fiberoptic light pipeline. The control unit 124 analyzes thebio-impedance information in combination with the spectrophotometricinformation are compared to threshold and/or historical stored values tomonitor tissue for detection and notification of tissue conditions suchas extravasation and infiltration.

[0063] In some embodiments, an infusion system 100 utilizes a pluralityof sensing technologies to improve reliability and reduce or eliminatethe occurrences of false alarms. The control unit 124 can utilizeinformation obtained using the multiple sensing technologies, store andanalyze a time history of the information using various techniques suchas thresholding and pattern recognition.

[0064] The infusion system 100 can be used to deliver fluid for variouspurposes including patient hydration, nutrient delivery, therapeuticdrug delivery, diagnostic testing, supply of blood components or otherhealthcare materials. During operation, the infusion device 110 deliversinfusion fluid through the flexible tubing 114 and the cannula 116 intothe patient's vascular system.

[0065] The infusion system 100 is suitable for use in any suitable IVsetting, such as routine patient care in medical surgical units,operating room ambulatory care centers, home healthcare for patientsundergoing intravenous therapeutic treatment, and others.

[0066] The control unit 124 obtains and stores information from thesensors 120. Depending on the particular sensing technology, the controlunit 124 may include various signal conditioners and processors toconfigure the information more suitably for subsequent analysis andstorage.

[0067] For some sensor technologies such as sensors that acquireelectrical information in one or more frequency bands, the control unit124 includes a multiple gain amplifier circuit. In one example, theamplifier circuit may have multiple filter stages (not shown) such as ahigh-gain stage, a medium-gain stage, and a low-gain stage connected ina cascade configuration. The cascaded filter is coupled to an analog todigital converter (not shown) that can convert the sensed informationfor analysis and storage under control of a processor (not shown).

[0068] The processor may be any suitable type such as a microprocessor,a controller a microcontroller, a central processing unit (CPU), adigital signal processor (DSP), a state machine, discrete logic, or thelike. The processor can be programmed to perform a variety of analysis,storage, and control functions. In one example, the processor includes aprogram for generating data images from processed signals that areindicative of tissue condition. The processor also includes a controlprogram for controlling signals acquisition by the sensors 120. Theprocessor may include a communication program for communicatinginformation to a remote location, enabling remote surveillance of tissuemeasurements and characteristics.

[0069] The infusion system 100 detects and monitors one or moreconditions including blood clots, phlebitis, tissue necrosis, andintravascular infiltration and extravasation associated with theinfusion of a flowable material in a vascular pathway. The infusionsystem 100, upon detection of one or more particular conditions, cangenerate a detection signal, a status and alarm notification, givingmedical surveillance of the status of tissue as a patient receives aninfusion. The surveillance signal notifies a health care provider orcaretaker to intervene early to avoid intravascular complications. Thealarm may be an audible sound, a warning screen display for a computer,a vibration or buzzer annunciation, flashing lights, or any othersuitable signal. The notification signal may be delivered to a proximalor remote location.

[0070] The control unit 124 may have an alarm or enunciator that enablesa caretaker, for example a nurse, positioned in a remote location tosupervise a patient's infusion. The infusion system 100 can beconfigured as a safe, efficient, inexpensive, and reliable monitoringdevice for early detection of infiltration, extravasation, and othercomplications that is suitable for use both inside and out of a hospitalenvironment. The sensor dressing 118 can be applied at the perivasculararea at the site of the intravascular insertion and also at bodylocations remote from the insertion that are at risk of fluid collectiondue to infiltration and extravasation.

[0071] In some embodiments, the control unit 124 is capable ofcommunicating with an infusion controller 132 that is a component of theinfusion device 110 to control an infusion pump 134. The infusion system100 monitors patient tissue condition and, under control of asurveillance program executing in the control unit 124, can detectharmful tissue conditions and reduce complications by adjusting infusionflow or terminate infusion in response to the alarm condition.

[0072] Referring to FIG. 2 in combination with FIG. 1, a schematic blockdiagram shows functional blocks of a physiological monitoring system 200for monitoring surface tissue and subcutaneous tissue with a capabilityto monitor tissue conditions. A tissue contacting section 118 contains asensor pathway and is attached to a control unit housing 124 by anumbilical cable 126. A fiber optic line 218 runs inside the umbilicalcable 126 and is connected through the tissue contacting section 118.

[0073] Various types of connectors may be used. Several suitableconnector types include zebra connectors, pin connectors, conductiveadhesives, a modified EKG snap that can be snapped onto a tailconnector, a Ziff connector, and others. Circuit connectors may beconnected by an interactive “tail” that exits the dressing eitherinternally or externally. Connections are commonly made by CTR-CTRDuPont® “clincher” or AMP® “multiple-crimp” connector. Interconnectionmay also be attained using CTR-CTR, PC board-mounted, slide-in, pressureconnectors, Elastomeric® “zebra-strip” connectors and “Z-axis-only”conductive adhesives. The wide range of connection selections addressspace and cost constraints.

[0074] An optical sensing system 210 includes an optical source 212 andan optical detector 214. The optical source 212 is known to those ofordinary skill in the optics arts and typically includes a time-gatingcircuit, a pulse synchronization circuit, and a gate switch coupled toan infrared generator. The optical detector 214 is known to those havingordinary skill in the optics arts and includes a photonics detectorcoupled to a processor 220 via an analog to digital converter.Information from the optical detector 214 can be shown on a display 216such as a liquid crystal display (LCD) module. Light from the opticalsource 212 is transmitted to the patient's skin via the fiber optic line218 and reflections from the skin are transmitted back to the opticaldetector 214 via the fiber optic line 218. The processor 220 can beconnected to an alert tone generator 222 to inform a caretaker or thepatient of an alert condition.

[0075] In the illustrative system, the processor 220 can communicatewith a visual screen 224 and pager 226 that are freestanding. A catheterand cable securement support (not shown) can be attached to the tissuecontacting section 118.

[0076] A polymer protein coating adhesive, hydrogel adhesives, andconductive ink sensor pathway are applied to the tissue-contactingsegment 118. A silver conductive ink adhesive can be applied in aselected configuration.

[0077] A caretaker uses the monitoring system 200 by applying the tissuecontacting segment 118 to the surface of a patient's skin at one or moremonitoring positions, including over the site of intravascularinsertion. A catheter and cable securement support is applied on anintravenous catheter used to deliver infusion material into thepatient's vascular pathway. The umbilical cable 126 attaches to thecontrol housing unit 124. The caretaker can activate the control unit byactuating an on-off switch (not shown).

[0078] The infrared generator sends near infrared signals through theinfrared delivery pipeline including the fiber optic line 218. Thesensor pathway for the optical light could be clear pipelines or freeair. The infrared detector responds to pulse excitations fromsubcutaneous and surface skin. Signals from the infrared detector aremonitored utilizing a multi-gain preamplifier circuit (not shown)connected to the output terminal of a photonics detector. A gate switch(not shown) connected to the output terminal of the multi-gainpreamplifier controls sampling of the photonics detector signals. Themultigain amplifier circuit connects to an integrator (not shown) tointegrate the acquired samples.

[0079] A time-gating circuit connected to a switch opens and closes theswitch at regular time intervals during signal monitoring. The pulsesynchronization circuit connected to the time-gating circuit supplies asignal to the time-gating circuit that indicates when the pulse isexpected to arrive at the photonics detector. Data from the opticaldetector 214 are collected, compared to control information, quantified,and analyzed to determine the presence or absence of conditions that mayindicate infiltration and extravasation.

[0080] The physiological monitoring system 200 may also include abio-impedance sensing system 230. The bio-impedance sensing system 230further comprises a current generator 232 and an ampere meter 234. Thecurrent generator 232 sends current through the hydrogel conductivesensor pathway to the tissue while an ampere meter 234 records datausing an analog to digital converter (ADC) and sends the information tothe processor 220. In another example the conductive pathway can beformed by small conductive silver wires. The processor 220 stores data,compares the data with preset information including threshold andpatterns to determine the presence of absence of conditions that mayindicate infiltration or extravasation.

[0081] The processor 220 combines the bio-impedance and opticalinformation and forwards information on tissue condition by a wirelessinterface card, for example, to one or more display screens. The displayscreens may include screens on a pager, a control unit visual displayscreen, a computer visual display screen and the like. In one example,information can be web enabled and sent via the Internet to a caregivervia personal digital assistant (PDA).

[0082] The hydrogel sensor conductive pathway uses adhesives of hydrogelconductive ink 238 to couple the tissue contacting segment 118 totissue. In a specific example, the adhesive is an adhesive of silverconductive ink.

[0083] The monitoring system can be configured as a highly reliable,lightweight, and economical device for monitoring the tissue conditionsand identifying complications that may occur during infusion. Acaretaker receives useful information to improve quality of patient carein the hospital, home care setting, chemotherapy clinic, or at anylocation.

[0084] Referring to FIG. 3, a pictorial diagram shows an example of asuitable film barrier dressing 300 for usage with an infusion system.The film barrier dressing 300 is a flexible membrane can be temporarilyattached to a patient's skin and later removed. The film barrierdressing 300 can be constructed from several flexible membrane materialssuch as breathable barrier films that supply moisture vapor permeabilitywhile preventing passage of liquids through the dressing. Typicalflexible membrane materials include microporous materials and densemonolithic membranes. Some of the membrane materials are useful forinfection control and pass water vapor while excluding or killingpathogenic microorganisms such as bacteria.

[0085] A microporous structure has capillary-like pores that inhibitliquid flow due to the small size of the pores and lyophobicity of thepolymer membrane material. Gases and vapors permeate a microporous filmby physical mechanisms based on pore size. If the diameter of the holesis less than the mean free path of the gas, individual molecules canpass but bulk gas flow is prevented. Physical structure rather thanpolymer chemistry determines permeability of microporous films, incontrast to dense monolithic membranes.

[0086] A dense monolithic membrane functions as an absolute barrier toliquid but has selective permeability to gases and vapors. The densemembranes are pinhole-free polymer membranes that transmit vapors andnoncondensable gases through activated diffusion resulting fromconcentration gradients within the membrane. Suitable polymers includenonpolar, nonhygroscopic polymers such as polyethylene andpolypropylene. Permeability is increased for variations in chemistry orstructure that increase diffusion constant and permeability.

[0087] Suitable barrier membrane materials include film dressings fromTyco Healthcare—U.S. Surgical of Norwalk, Conn., Tegaderm™ and padtransparent dressing from 3M of Minneapolis, Minn., and dressings fromProtein Polymer Technologies, Inc. of San Diego, Calif. , transparentfilms that function in the manner of artificial skin. For example,suitable film dressings are secure dressings that are transparent forviewing the puncture site and condition of surrounding skin, whilepreventing proliferation of bacteria.

[0088] The film barrier dressing 300 has a laminar structure comprising,for example, a base film 312, an adhesive layer 314 coupled to anapplication side of the base film 312 and a foam layer 316 coupled tothe base film surface opposite the adhesive. Coupled to the foam layer316 is a conductive ink layer 320 that is patterned to form electricallyconductive lines. In one example, the conductive ink is composed ofsilver/silver chloride although other conductive materials may be usedincluding carbon, gold, electrically conductive composites, metallics,conductive polymers, foils, films, inks, or any forms of thermistorcatheters. Other suitable conductive materials include wires, platinum,aluminum, silicone rubber conductive materials with nickel-graphitecompounds, nanopowders and proteins, graphite conductive wires, and thelike. A dielectric insulator 321 separates the conductive ink layer 320in a selective manner and prevents migration of conductive materials.

[0089] A hydrogel layer 322 overlies the foam layer 316 and thepatterned conductive ink layer 320. A film release liner 324 is coupledto the hydrogel layer 322 for application of the film barrier dressing300 to the patient's skin. A plurality of electrodes 330 are patternedin the conductive ink and also in conductive portions of the adhesiveand integrated hydrogel to make contact with the patient's skin. Theconductive ink layer 320 is patterned to form conductive lines in thefilm barrier dressing 300 that extend to a terminal strip 334 withcontacts 336 for connecting to communication lines in a cable forcommunicating with a control unit. In one example, the control unitcommunication lines electrically connect to the contacts 336 using aclip 338 containing terminals capable of supplying an energizing signalto the electrodes 330. A connecting pad (not shown) in combination withthe dielectric insulator 321 supply insulation and protection againstmigration of conductive material in the cable containing the conductivecircuit and at a junction of the connecting pad and the cable.

[0090] In some embodiments, the film barrier dressing 300 utilizes aconductive ink layer 320 in which a silver conductor is cured on amaterial that can be affixed to tissue. The silver conductor is screenprinted on a flexible material. The silver conductor can utilize apolymer thick film composition such as polyester, polyamide,polycarbonate, and epoxy glass. The silver chloride ink is ink printedon the sensor system material.

[0091] The film barrier dressing 300 includes a frame 310 and a flexibleprotective film 332. In the illustrative example, the frame 310 extendsalong peripheral edges of the film barrier dressing 300 leaving aninterior void, and the flexible protective film 332 is attached to theframe 310 and extends over the interior void. The electrodes 330 may beformed in the frame 310, the flexible protective film 332 or both.

[0092] The interior void is typically sufficiently large to allowvisualization through the patient's skin. The frame 310 can be composedof any material with suitable flexibility, strength, and hygienicproperties. A suitable frame material is Melinex from Tekra Corporationof New Berlin, Wis. Although the frame 310 is depicted as rectangular ingeometry, any suitable shape may be used including circular, oval,triangular, or any other shape. The electrodes 330 are typicallyconfigured as two or more electrode pairs. For example, so thatalternating electrical energy may be applied to a first pair ofelectrodes to generate an electric field to induce a signal in a secondelectrode pair. The generated field is a function of the impedance ofthe tissue.

[0093] The electrodes 330 can be flexibly formed in various suitableconfigurations to facilitate detection of selected signals. Theelectrodes 330 can be patterned in selected shapes by laminatingalternating planes of conductive ink layer 320 and layers of dielectricinsulator 321. For example, conventional semiconductor laminatingtechniques can be used to form electrodes 330 of desired geometries. Insome particular examples, coil electrodes can be manufactured byselective patterning of multiple layers, with individual layers having apatterned conductive ink layer 320. Overlying and underlying patterns inthe conductive ink layer 320 form the coils. Coil electrodes generate afavorable current density distribution for electrical measurements. Coilelectrodes commonly interrogate in a frequency range of 1 MHz to 10 MHzto attain good depth sensitivity. In contrast contact electrodesgenerally operate in a frequency range from about 10 kHz to 100 kHz. Invarious systems, the coils may have different configurations. Some coilsare contact coils that are placed in contact with the skin, other coilsare noncontact coils that are removed from the skin by a predetermineddistance.

[0094] A control unit communicates with the electrodes 330 in the filmbarrier dressing 300 to gather and process information for determiningtissue impedance. The control unit determines the occurrence ofextravasation analyzing tissue impedance measurement patterns in timeand space, thereby enabling early detection.

[0095] In an example of a tissue impedance measuring operation, acaretaker affixes the film barrier dressing 300 so that the electrodes330 enclose the tip of the needle or catheter and extends up toapproximately three inches. The extended film barrier dressing 300 canmonitor tissue in the area of the insertion site of the vascular accessdevice and surrounding perivascular tissue. The control unit applies avoltage across a first pair of electrodes to induce a signal in a secondpair of electrodes and measures impedance at the second pair ofelectrodes. The control unit stores the impedance measurements over timeand determines changes in the impedance from a baseline measurementtaken prior to commencing the injection procedure.

[0096] The infusion system is typically used to detect IV complicationsby introducing a cannula or needle into the patient's vascular system,removing the film release liner 324 and attaching the film barrierdressing 300 to the patient's skin using the adhesive layer 314. Thefilm barrier dressing 300 is positioned so that the needle tip iscovered by the void interior to the frame 310.

[0097] The film barrier dressing 300 functions as a securement systemthat is adaptable to cover a suitable size area of tissue. In oneexample, the film barrier dressing 300 is a flexible material that isadaptable to cover an area of approximately 1×1 inch or extendable toapproximately 3×8 inches. Typically, the smaller patch can be used tomonitor at the infusion site and the larger patch can be used at anysuitable location on the body.

[0098] In some embodiments, the film barrier dressing 300 may include apolymer delivery system with a topical antiseptic applied for deliveringtopical antibiotics. The topical antiseptic is delivered over time withelectrical current applied to the electrodes to enhance antibioticdelivery and increase penetration of the antibiotic through the skin.

[0099] In a specific example, a dressing may include lidocaine fortopical application. In some systems, the antiseptic may be applied tothe dressing prior to application to the patient's skin, for example, asa manufacturing step. In other systems, the dressing is applied to thepatient's skin without the antiseptic so that baseline sensormeasurements may be acquired. The antiseptic may then be applied laterto better track changes that result from the therapy.

[0100] Referring to FIG. 4, a schematic pictorial diagram illustrates anexample of a suitable electrical signal sensor 400 that is capable ofmeasuring bio-potentials, bio-impedances, electrical impedances, and thelike for usage in an infusion monitoring device. The illustrativeelectrical signal sensor 400 is a plethysmograph that can be applied toa patient's appendage to detect extravasation, infiltration, phlebitis,or other conditions during injection of fluid into the patient's bloodvessel. Typically, an electrical impedance sensor 400 is positioned sothat the geometric center of multiple sensor elements corresponds to thelocation of the injection site.

[0101] The illustrative electrical impedance sensor 400 has sixelectrodes 410. Other examples of a suitable sensor may have fewerelectrodes or more electrodes. The electrodes 410 may be constructedfrom a silver/silver chloride mixture or other suitable conductivematerial. The illustrative electrodes 410 include three stimulatingelectrodes 418 and three receiving electrodes 416.

[0102] The electrodes 410 can be positioned, if possible, in directohmic contact with the patient's skin or, otherwise, capacitivelycoupled with a slight offset from the skin in the vicinity of theinjection site.

[0103] The electrical impedance sensor 400 includes a current source 412for applying a current to the injection site via the stimulatingelectrodes 410 and a high impedance amplifier 414 that is connected tothe two receiving electrodes 410 and receives and amplifies the voltagedifference between the receiving electrodes 416. The current source 412typically injects radio frequency (RF) energy in a suitable range offrequencies, for example from one kilohertz to about one megahertz.

[0104] Extravasation causes a volume change due to tissue swelling and aconductivity change which, in combination, change the electricalimpedance sensed by the receiving electrodes 416. An impedance variationmodifies the voltage detected by the high impedance amplifier 414,permitting extravasation detection, notification of IV complications ofinfiltration, extravasation, and other conditions, and intervention, forexample by terminating IV application.

[0105] The electrodes 410 can be positioned on the surface of a highdielectric layer (not shown) to attain efficient capacitive coupling tothe patient. A hydrogel layer (not shown) coupled to the high dielectriclayer on the surface for application to the patient's skin may be usedto improve electrical coupling of the electrodes 410 to the patient.

[0106] A low dielectric layer (not shown) coats the electrodes 410 andthe high dielectric layer and functions as a substrate for applying theelectrodes 410 to the patient. A high conductivity layer (not shown)coats the low dielectric layer and functions as a ground plane for theelectrical impedance sensor 400 that shields the electrodes 410 fromstray capacitance, improving impedance measurement reliability.

[0107] Although the illustrative electrical impedance sensor 400 has sixelectrodes 410, additional electrodes may be added in variousconfigurations to attain additional functionality. For example, thesix-electrode electrical impedance sensor 400 may be more suitable fordetecting extravasation and infiltration in the vicinity of the infusionsite and collection of fluid due to dependent edema. Additionalelectrodes may be added to detect extravasation and infiltration at aposition remote from the insertion, for example due to valve disease orweakening of vessel walls. The additional electrodes in combination withthe electrodes 410 may be arranged in various configurations to extenddiagnostic performance. Alternatively, additional electrical impedancesensors may be used to detect remote extravasation. For example, theelectrodes may be arranged in an annular array configuration or a lineararray configuration. In one example, two outer electrodes may beconnected as a source and sink of RF current, while any two electrodespositioned between the source and sink can be used to measure current,voltage, or impedance. Switches and processing electronics (not shown)can be used to sample from selected inner electrodes to senseextravasation and infusion at multiple positions along the bloodvessels.

[0108] In some embodiments, sampling of various positions may bemodified over time to sample predominantly in the vicinity of theinjection in the early IV stages and to sample to detect remoteextravasation in later stages when more likely to occur.

[0109] The electrical impedance sensor 400 is useful for monitoringintravascular infiltration and extravasation. Intravascular infiltrationand extravasation may alter histological and biochemical tissueconditions in intracellular and extracellular fluid compartments, cellmembrane surface area, macromolecules, ionic permeability, andmembrane-associated water layers. The histological and biochemicalchanges within the infiltrated tissue or area of infiltration andextravasation result in a measurable change in tissue electricalimpedance.

[0110] In some embodiments, the electrical impedance sensor 400comprises a plurality of transducers to generate one or more sensorpathways utilizing depth-selective sensing of tissue bio-impedance in adesired frequency range. The bio-impedance sensor 400 generatescross-sectional surface measurements and subcutaneous measurements atone or more selected tissue depths by controlling the field extension ofthe sensor pathway. Interrogation of various depths occurs by samplingat electrodes positioned at multiple locations, using electrodesconstructed from various different materials, interrogating using amultiple array transducer configuration, and interrogating at variousselected frequencies or with various selected interrogation waveforms.

[0111] In a particular example, the electrical impedance sensor 400 fastreconstruction technique applies currents to the body surface andmeasures resulting surface potentials using a. The fast reconstructiontechnique presumes that a linear dependence exists between the smalldeviation in impedance and the corresponding change of surfacepotentials. The geometry of the internal organs or tissue is known sothat initial conductivity estimates are presumed known. A sensitivitymatrix encodes the presumed impedance values and conductivity changesare found by inverse-matrix multiplication.

[0112] Under processor control, the electrical impedance sensor 400applies currents to selected electrodes on the body surface and measuresresulting surface potential distributions from the electrodes. Thesensitivity matrix A describes the dependence between small deviationsof conductivity and a change of measured surface potentials according toequation (1) in which Δσ is the vector of the individual conductivitydeviations and Δφ describes changes of measured surface potentials:

Δφ=A·Δσ  (1)

[0113] Knowledge of the sensitivity matrix for a model organ or tissuegeometry and electrode arrangement permits determination of conductivitydeviations according to equation (2) in which A⁻¹ is the pseudoinverseof matrix A determined using singular value decomposition:

Δσ=A⁻¹·Δφ  (2)

[0114] The sensitivity matrix A can be determined by simulatingmeasurements using conductivity values obtained from literature orexperiment. In some applications, conductivity values can be graduallychanged and surface potential distributions can be measured for thedifferent conductivity values to determine the column values for thematrix. In alternative examples, sensitivity can be directly calculatedusing a more efficient finite element analysis discussed hereinafterwith respect to FIGS. 12 to 17.

[0115] The electrode pattern and position are selected for theparticular tested organ or tissue, depending on the geometry andconductivity distribution of normal and abnormal tissue, and optimizedto generate the maximum voltage difference between the normal andabnormal case.

[0116] The electrical impedance sensor 400 includes multiple sets ofelectrodes and the pattern of excitation current and electrode shape andposition is defined based on application. The electrical impedancesensor 400 is configured to recognize objects in a formal known positionaccording to conductivity data measured for normal tissue. Accordingly,test measurements of current density distribution in normal and abnormalcases are stored and compared with test measurements to classify thetissue under test.

[0117] Some embodiments may use one large electrode and a plurality ofsmall electrodes. Measurements may be made at one or more testfrequencies depending on the impedance frequency spectrum of themeasured tissue. Pattern recognition is made based on modeling ofelectric fields and current density using sensitivity analysis forpattern recognition in three dimensions and finite element analysis. Invarious embodiments, linear inversion or nonlinear inversion may be usedfor pattern recognition.

[0118] In some embodiments, a control unit obtains and compares thebio-impedance measurements to measurements acquired using a secondtechnology. For example, an optical sensor can be used to detect a lightreflection pattern generated by an infrared light source. Otherembodiments may use only a single measurement technology.

[0119] In another example of a fast bioimpedance tomography technique,tissue impedance maps are constructed from surface measurements usingnonlinear optimization. A nonlinear optimization technique utilizingknown and stored constraint values permits reconstruction of a widerange of conductivity values in the tissue. In the nonlinear system, aJacobian Matrix is renewed for a plurality of iterations. The JacobianMatrix describes changes in surface voltage that result from changes inconductivity. The Jacobian Matrix stores information relating to thepattern and position of measuring electrodes, and the geometry andconductivity distributions of measurements resulting in a normal caseand in an abnormal case. The objective of the nonlinear estimation is todetermine the maximum voltage difference in the normal and abnormalcases.

[0120] In another example of a sensing technology using bio-potentialmeasurements, the electrical signal sensor 400 may measure the potentiallevel of the electromagnetic field in tissue. A suitable bio-potentialsensor includes a reference electrode and one or more test electrodes.In some systems, the test and reference electrodes may beinterchangeable, for example under control of a processor, to vary thedesired tissue measurement field.

[0121] The sensor may be any suitable form of electrode 410. In oneexample, the electrodes 410 are predominantly composed of a silverchloride (AgCl) layer coupled to an electrode lead by a silver (Ag)layer. The tissue contact surface of the electrode is a concentratedsalt (NaCl) material coupled to the AgCl layer. The electrode may alsoinclude an insulated housing that covers the AgCl layer, the Ag layer,and the end of the lead to reduce electromagnetic interference andleakage.

[0122] The patient's tissue generates an electromagnetic field ofpositive or negative polarity, typically in the millivolt range. Thesensor measures the electromagnetic field by detecting the difference inpotential between one or more test electrodes and a reference electrode.The bio-potential sensor uses signal conditioners or processors tocondition the potential signal. In one example, the test electrode andreference electrode are coupled to a signal conditioner/processor thatincludes a lowpass filter to remove undesired high frequency signalcomponents. The electromagnetic field signal is typically a slowlyvarying DC voltage signal. The lowpass filter removes undesiredalternating current components arising from static discharge,electromagnetic interference, and other sources.

[0123] Another example of a sensing technology employs noninvasivedepth-selective detection and characterization of surface phenomena inorganic and biological material by surface measurement of the electricalimpedance of the material where the device utilizes a probe with aplurality of measuring electrodes separated by a control electrode. Moreparticularly, the impedance sensor comprises a measuring electrode 412structure with triple annular concentric circles including a centralelectrode, an intermediate electrode and an outer electrode. Allelectrodes can couple to the skin. One electrode is a common electrodeand supplies a low frequency signal between this common electrode andanother of the three electrodes. An amplifier converts the resultingcurrent into a voltage between the common electrode and another of thethree electrodes. A switch switches between a first circuit using theintermediate electrode as the common electrode and a second circuit thatuses the outer electrode as a common electrode.

[0124] The sensor selects depth by controlling the extension of theelectric field in the vicinity of the measuring electrodes using thecontrol electrode between the measuring electrodes. The controlelectrode is actively driven with the same frequency as the measuringelectrodes to a signal level taken from one of the measuring electrodesbut multiplied by a complex number with real and imaginary partscontrolled to attain a desired depth penetration. The controlling fieldfunctions in the manner of a field effect transistor in which ionic andpolarization effects act upon tissue in the manner of a semiconductormaterial.

[0125] With multiple groups of electrodes and a capability to measure ata plurality of depths, the sensor has a capability of tomographicimaging or measurement, and/or object recognition. Other implementationsthat use fewer electrodes and more abbreviated, fast reconstructiontechnique of finite-solution pattern recognition, can be constructed insmaller, more portable systems. Conventional tomography techniques arecomputation intensive and typically require a large computer. Althoughthese computation intensive techniques can be used to implement thedisclosed system, other techniques with a lower computation burden maybe used, such as the fast reconstruction technique. The fastreconstruction technique reduces computation burden by utilizing priorinformation of normal and abnormal tissue conductivity characteristicsto estimate tissue condition without requiring full computation of anon-linear inverse solution.

[0126] Referring to FIG. 5, a schematic block diagram illustratesanother example of an electrical signals sensor in the configuration ofan electrode array sensor 500. The electrode array sensor 500 is usefulfor sensing techniques including impedance, bio-potential, orelectromagnetic field tomography imaging of tissue. The electrode arraysensor 500 comprises an electrode array 510 is a geometric array ofdiscrete electrodes. The illustrative electrode array 510 has anequal-space geometry of multiple nodes that are capable of functioningas sense and reference electrodes. In a typical tomography applicationthe electrodes are equally-spaced in a circular configuration.Alternatively, the electrodes can have non-equal spacing and/or can bein rectangular or other configurations in one circuit or multiplecircuits. Electrodes can be configured in concentric layers too. Pointsof extension form multiple nodes that are capable of functioning as anelectrical reference. Data from the multiple reference points can becollected to generate a spectrographic composite for monitoring overtime

[0127] In an illustrative example, the electrode array 510 is configuredto function as one or more measurement channels. An individual channelincludes one or more electrodes that supply current to the tissue at aselected frequency and selected waveform morphology. Another electrodein the channel is a sensing electrode that senses the voltage generated.

[0128] Alternatively, the array may take any suitable form including arectangular, square, circular, oval, triangular, or any othertwo-dimensional shape. The array may include peripheral array elementswith central elements omitted, or take any shape with any patterns ofinner or peripheral elements omitted.

[0129] Electrode spacing configurations are predetermined according tothe spatial frequency of the detected electric field potential.

[0130] Spatial tomography imaging of tissue using detected electricalparameters generally involves spatial deconvolution of detected signalsto reconstruct electrophysiological patterns from detected surfacesignals.

[0131] Individual electrodes in the electrode array 510 are coupled to asignal conditioner/processor including preamplifiers 512 for high gainamplification at high input impedance, low current loading, and lownoise. The preamplifiers 512 may be configured to function as a bandpass filter or the signal conditioner/processor may include a band passfilter 514 to confine signals to a desired frequency band. Band passfiltered signals are applied to a multiplexer 516 that can be part ofthe signal conditioner/processor to sequentially sample amplified andfiltered analog signals from individual electrodes in the electrodearray 510.

[0132] Analog signals from the multiplexer 516 are digitized by an A/Dconverter 518 that sequentially samples signals from the individualelectrodes of the electrode array 510.

[0133] Digital signals from the A/D converter 518 can be applied to aprocessor 520 for analysis, storage 522, and/or display 524. Theprocessor can execute a variety of functions such as computing a spatialdeconvolution transformation of detected electrode field potentials.

[0134] In another example of the electrode array sensor 500, theelectrodes can be arranged as one or more sets of electrode groups. Anelectrode group includes three pairs of electrode. A first electrodepair is excitation electrodes, a second pair is sensing electrodes, anda third pair is focusing electrodes. The focusing electrodes focuscurrent flowing between the excitation electrodes to the sensingelectrode region.

[0135] The excitation electrodes and the sensing electrodes are spacedso that the sensing electrodes are capable of measuring the voltage dropbetween the sensing electrodes that occurs as a result of an excitationpulse at the excitation electrodes. The focusing electrodes focus thecurrent flowing between the excitation electrodes to the sensingelectrode region. In one example, the focusing electrodes are planarelectrodes, aligned and on opposite sides of the line between the twoexcitational electrodes.

[0136] Referring to FIGS. 6A and 6B, block diagrams illustrate anexample of an additional electrical signal sensing technology, anelectric signal tomogram scanner 600 that may be used in embodimentswith extensive computation capabilities. Other implementations that usemore abbreviated fast reconstruction technique of pattern recognition,can be constructed in smaller, more portable systems. The electricsignal tomogram scanner 600 comprises a signal generator 610, aplurality of boundary condition modules 612, a plurality of dataacquisition modules 614, and an electrode array 616. The electric signaltomogram scanner 600 receives control signals from a processor via aninterface 618. The signal generator 610 supplies signals to the boundarycondition modules 612 that communicate with corresponding dataacquisition modules 614 to drive the electrode array 616. A dataacquisition module 614 drives a plurality of electrode elements in theelectrode array 616. A particular combination of a boundary conditionmodule 612 and a data acquisition module 614 generates boundaryconditions and measures resultant voltage drops across small sensingresistors (not shown) to measure electrical signals at the individualelectrodes in the electrode array 616.

[0137] The signal generator 610 supplies a sinewave voltage of suitablefrequency, for example between 100 Hz and 1 KHz to a multiplying digitalto analog converter (DAC) 620, generating a voltage drop across resistor622 and instrumentation amplifier 624 in a data acquisition module 614.

[0138] In one example, the signal generator 610 comprises acrystal-controlled oscillator (not shown) coupled to a frequency divider(not shown) that reduces the oscillator frequency. The frequency divideris in turn coupled to a phase splitter (not shown) that produces afurther divided signal as one-quarter cycle displaced square waves. Thephase splitter supplies the quarter-cycle displaced square wave signalsto a delay line (not shown) and to a high Q bandpass filter (not shown).The bandpass filter is coupled to a buffer amplifier (not shown) togenerate a sinewave signal psin2ηt where η is the square wave frequency.An in-phase squarewave, a quadrature squarewave and subconjugates aredelayed by the digital delay line to compensate for delay through thebandpass filter and the buffer amplifier. Four phases of the sinewaveoccur at positive transitions of the squarewave signals and passed tothe interface 618.

[0139] A sample and hold circuit 626 receives the amplified signal andsupplies samples to an analog to digital converter (ADC) 628, timedaccording to clock signals from the signal generator 610. ADC 628supplies digital signals indicative of current measurements at theelectrode in the electrode array 616.

[0140] Electrodes receive a boundary condition that establishes avoltage across the resistor 622. The data acquisition modules 614 firstproduce a controlled voltage at electrodes in the electrode array 616 toestablish a boundary condition, then measure resulting voltages toenable boundary current computation.

[0141] In some embodiments, a processor controls the electric signaltomogram scanner 600 to apply a voltage distribution over some externalboundary of an object and find the current flow at the boundary from asolution of Laplace's equation to reconstruct the distribution ofelectrical properties within the object. The process involvespositioning a three-dimensional electrode array 616 about the object,applying selected voltages to a selected first set of electrodes andmeasuring currents through a selected second set of electrodes, whichmay include some or all of the first set.

[0142] The electric signal tomogram scanner 600 imposes a virtualthree-dimensional grid onto the object at a selected resolution levelwith each node of the grid allowed to assume an independent electricalparameter. The scanner determines a best value for the electricalparameter for each node without any preconditions. The electric signaltomogram scanner 600 then performs an iterative process to determine aspecific distribution of electrical properties at the grid nodes to mostclosely match the measured currents at the boundary and the currentsbased on the specific distributions.

[0143] In the illustrative electric signal tomogram scanner 600, theboundary condition modules 612 and the data acquisition modules 614 areidentical except that the boundary condition modules 612 store presetboundary conditions in a nonvolative memory.

[0144] Referring to FIG. 7, a schematic pictorial diagram shows anexample of a suitable temperature sensing device 700 for usage in theinfusion system. The illustrative temperature sensing device 700 is abiomedical chip thermistor assembly that is useful both for intermittentand continuous monitoring. The thermistor 700 includes a stainless steelhousing 710 that is suitable for reusable and disposable applicationsand has a nominal resistance value that ranges from approximately 2000 Ωto about 20,000 Ω at 25° C. The thermistor body 712 including wires 714and sensor tip 716 can be composed of stainless steel. The wires 714 areinsulated using a suitable material such as medical grade PVC teflon. Inother examples, the body material can be composed of materials such aslexan for the wires 714 or shaft and an aluminum tip, or molded plasticor kapton. Other suitable insulating materials include teflon, heavyisomid, or polyurethane with a nylon coat. The thermistor 700 is anelectrical circuit element that is formed with semiconducting materialsand is characterized by a high temperature coefficient. The thermistor700 functions as a resistor with a temperature coefficient rangingtypically from about −3 to −5%/° C. The thermistor can be activatedusing either current or voltage excitation. The thermistor 700 isconnected via the wires or shaft to a high resolution analog to digitalconverter. Thermistors are non-linear devices so that linearizationtechniques are typically used to obtain accurate measurements.

[0145] Referring to FIG. 8, a schematic pictorial diagram depicts asuitable optical sensor 800 for usage with the infusion system. In oneexample, the optical sensor 800 is an infrared light emitting diode(LED)/phototransistor pair that can sense detectable variations in skincharacteristics. The optical sensor 800 comprises an emitter or infraredtransmitter (LED) 810 and a photonics or retrosensor detector 812 thatmeasure light reflections to derive data points. When gently pressedagainst the skin radiation from the transmitter 810 through across-section of tissue including surface and subcutaneous tissuereflects back into the detector 812. Retrosensor detector 812photocurrent detects the infrared signal and produces an ac signalacross transistors Q2 and Q3 of about 500 uV peak to peak for a 1%change in skin reflectance, a logarithmic relationship that is constantover many orders of photocurrent magnitude. Therefore reliable circuitoperation is possible despite wide variation in skin contrast and lightlevel. Signals from the transistors Q2 and Q3 are applied to a high-gainadaptive filter 814 that rejects ambient optical and electrical noiseand supplies a clean signal to comparator 816 to extract a digitalsignal.

[0146] Referring to FIG. 9, a schematic block diagram illustrates anexample of a control unit 900 suitable for usage with the illustrativeinfusion system. The control unit 900 is contained in a housing (notshown) and attaches to one or more sensors 910, 912, and 914 fordetecting various physiological signals. Although the illustratedexample depicts three sensors, a single sensor or any suitable number ofsensors may be implemented depending on the particular parameters to besensed for an application. One example of a suitable system includes abio-impedance sensor 910, an optical sensor 912, and an ultrasoundsensor 914. Other types of sensors may replace the illustrative sensorsor be used in addition to the illustrative sensors. Other suitablesensors include, for example, a flow sensor that senses infusion fluidflow, a pressure sensor, a thermistor, thermometer or other temperaturesensing device.

[0147] In some embodiments, biosensors can be incorporated into layersof the flexible dressing material. For example, Dupont MicrocircuitMaterials of Research Triangle Park, N.C. Biosensor materials can beincorporated into the flexible dressing material layers in variousgeometries using screen printing of conductive inks. Note that otherembodiments may utilize more conventional die-cut foils. The conductiveinks are highly suitable and permit high-speed, high-volume productionusing commercially-available production equipment.

[0148] The conductive inks are typically silver, gold, and carbon inkscomposed of thermoplastic polymer-based materials that are screenprinted and dried or cured. When the ink is dried and all solvent isremoved, the printed area becomes electrically conductive or insulative.The inks carry electrical current from a power supply to an active areaof the biosensor. Cured inks have useful properties of low resistivityand thus high conductivity permitting low voltage applications,flexibility, and adhesion.

[0149] Because the different inks have varying resistivities, forexample gold having a lower resistance than silver, which has lowerresistance than carbon, the inks can be selected to achieve selectedcircuit performance. Carbon ink can be used as an overprint for silverinks to prevent silver migration from two adjacent traces that carrydifferent amounts of current or potential, achieving a battery effect.

[0150] The conductive inks are highly adhesive to various substratematerials such as polyester, or Cetus fabric, a polyester substratesupplied by Dynic USA Corporation of Hillsboro, Oreg. Cetus is typicallya white backing material for the flexible dressing, upon which silverconductive ink can be printed. Other suitable substrate materialsinclude Polyester, Mylar or Melarax. Printable inks are suitable forusage on a polyester substrate that is print-treated andheat-stabilized.

[0151] Polymer thick film (PTF) inks contain a dispersed or dissolvedphase and attains suitable final properties simply by drying. Whenprinted and cured on a substrate, a particular electronic or biologicalfunctionality develops in the dried film. Suitable substrate includepolyester films such as DuPont TeijinT Mular® or Melinex®, or ceramicGreen TapeT. PTF products applied to flexible substrates are compact,lightweight, environmentally friendly, inexpensive, and permit efficientmanufacturing techniques. PTF films can be folded, twisted, bent aroundcorners, or bonded to any surface, permitting flexible application. PTFfilms are suitable for small features and layers can be printed inlayers to develop multiple functions. Polymer thick film technology ishighly suitable for printing electrodes and other components ofdisposable biosensors.

[0152] The conductive inks are flexible to prevent creasing that canincrease electrical resistance or cause cracking or delamination of thedressing when stretched. The flexible dressing material in combinationwith the conductive ink conforms to the body and allows stretchingwithout breaking the electrodes or increasing electrical noise.

[0153] Silver/silver chloride (Ag/AgCl) inks are used to deliver drugsor anesthetic through the skin using iontophoresis. The resistance ofsilver/silver chloride inks used for the electrodes is typicallyselected to be higher than the silver inks used for electricalconnections to restrict the current flowing through the electrodes tolow levels suitable for iontophoresis and to facilitate control ofiontophoresis. Printing selected amounts of the ink directly over silvertraces controls the resistance of silver/silver chloride inks. Thedesired surface area, iontophoresis rate, and duration of drug deliveryare taken into consideration in selection of the size and thickness ofAg/AgCl traces. The stability and reactivity of the drug and/or size ofthe drug molecule determine applicability for iontophoresis sinceinterstitial areas between skin cells can only be expanded to a limitedpoint with electrical current before irritation occurs.

[0154] Other sensors, ampermetric sensors, can be incorporated into theflexible dressing to measure concentration of various substances such asglucose, carbon dioxide, oxygen, and others. For example, a glucosesensor incorporates an enzyme into the dressing that reacts withextracted metabolic analytes such as glucose. The reaction creates asmall electrical charge that is proportional to the metabolic reactionrate An electrode indicates the electrical charge and a sensing circuitconverts the electrical charge to a numeric value that can be displayed,analyzed, stored, or the like. The flexible dressing typically includesa hydrogel that stores the enzyme or reagent. The sensor can functionusing reverse iontophoresis in which silver (Ag) ions move from anode tocathode extracting the metabolic analyte from the body and collected ina hydrogel pad. An electrode, for example a platinum-based electrode,can be used to read the current and function as a catalyst to drive thereaction between enzyme and glucose. Some ion-selective permeabilityinks also include a carbon component.

[0155] Other sensors, for example potentiometric sensors orelectrochemistry sensors, can be used to test electrolytes for examplepotassium (K) and other selective ions. Inks for sensing electrolytestypically include carbon with a platinum catalyst reagent as an ionselective sensor. Potentiometric sensors measure the voltage gradientacross a metabolic sample according to the sample's level ofconductivity at a selected voltage according to a calibrated standard.The lower the conductivity of the sample, the higher the voltage fordelivering a particular fixed current. Some potentiometric sensors usean ion-selective membrane ink printed over the electrodes to filterother analytes that contribute to high background noise.

[0156] Dielectric or encapsulant inks are insulators that protectadjacent traces from short-circuiting. The dielectric or encapsulantinks also assist adhesion. Some dielectrics can be used as capacitors tocreate circuits in combination with resistors formed by variousresistive inks inside the dressing. Capacitors within the dressingfacilitate storage and release of electric current pulses. Ultravioletdielectrics can be used to define active sensing areas of an electrode,limiting the surface area of blood or analyte to a selected size.

[0157] In other examples, the sensors may include biosensors composed ofnanostructured porous silicon films. Film biosensors detect analytebinding processes using a silicon-based optical interferometer. Thenanostructured porous silicon films are prepared by an electrochemicaletch of single crystal silicon substrates. The biosensor samples areprepared so that the porous silicon films display Fabry-Perot fringes intheir white-light reflection spectrum. Biological molecules arechemically attached as recognition elements to the inner walls of theporous silicon matrix. The film is exposured to a complementary bindingpair, causing binding and resulting in a shift in Fabry-Perot fringes.Analyte binding may be indicative of infiltration or extravasation.

[0158] The individual sensors 910, 912, and 914 may be connected withcorresponding respective signal conditioners or processors 916, 918, and920 in the control unit 900. In the illustrative example, thebio-impedance sensor 910 is coupled to a bio-impedance signalconditioner/processor 916, the optical sensor 912 is coupled to aninfrared signal conditioner/processor 918, and the ultrasound sensor 914is coupled to an ultrasound signal conditioner/processor 920. Althoughthe illustrative example, depicts sensors that are respectively coupledto particular signal conditioners or processors, in other examples twoor more sensors may share a particular signal conditioner/processor. Insome examples, a signal conditioner/processor may be dedicated to aparticular sensor and also use other signal conditioners/processors thatmay be shared among sensors. For some sensors, the signal from thesensor is suitable without processing or conditioning so that no signalconditioner/processor is utilized.

[0159] In the illustrative example the sensors 910, 912, and 914 and thesignal conditioners or processors 916, 918, and 920 are analog sensorsand conditioner/processors so that the signals from the signalconditioners or processors 916, 918, and 920 are applied to an analog todigital (A/D) converter 922 to convert the analog signals to digitalform. In other examples, one or more of the sensors orconditioner/processors may generate digital signals, bypassing the A/Dconverter 922. The signal conditioners or processors 916, 918, and 920may include or omit various elements such as amplifiers, filters,switches, and the like.

[0160] Digital signals from the A/D converter 922 and/or one or more ofthe sensors 910, 912, and 914 may be stored in a memory 924 and/or otherstorage device, or supplied directly to a processor 928, for exampleunder control of the processor 928 or controlled remotely from a remotecontrol and communication device (not shown). Alternatively, signalsfrom the A/D converter 922 and/or the sensors 910, 912, and 914 may becommunicated to a remote receiving device 930 via a transmitter/receiver934 for storage or analysis. Any suitable storage device 924 may be usedsuch as semiconductor memory, magnetic storage, optical storage, and thelike.

[0161] The memory can also be used to store various sensor and controlinformation including historical information and current informationacquired in real time.

[0162] In some examples, the control unit 900 may include a clockgenerator to supply a digital clock signal to correlate signals from thesensors 910, 912, and 914 to time. The A/D converter 922 and/or thesensors 910, 912, and 914 supply signals for storage or analysis at asuitable frequency. For many sensors, a suitable sample frequency may bein a range from 1 to 100 Hertz, although lower or higher samplefrequencies may be used. A suitable sample frequency is defined to besufficiently above a Nyquist sample rate of all signal frequencies ofinterest.

[0163] The processor 928 may be any suitable processing device such as acontroller, a microcontroller, a microprocessor, a central processingunit (CPU), a state machine, a digital logic, or any other similardevice. The processor 928 typically executes programs, processes,procedures, or routines that control various aspects of signalacquisition, analysis, storage, and communication. The processor 928 ispowered by a power source 906 that also supplies energy to othercomponents inside the housing 908 and to the sensors.

[0164] The filtered signal is input to the A/D converter 922 to convertthe signal to a form usable by the processor 928. Processor 928 performsoperations that convert the digital signal to one or more of severaluseful parameters indicative of the electromagnetic field. In oneexample, the processor 928 can sum the normalized values of the digitalsignals to generate an average or mean signal or determine changes inpolarity of the signal. The processor 928 can determine a plurality ofparameters, analyze the interrelationship of two or more parameters,detect variations of parameters over time, and the like.

[0165] The processor 928 acquires a plurality of electromagnetic fieldsamples for a period of the electromagnetic field, and normalizes andsums the values to compute an average or mean value for the period.

[0166] Referring to FIG. 10, a schematic pictorial view shows an exampleof a control unit 900 that is configured to be attachable to a patient'sarm or leg for monitoring of extravasation, infiltration, phlebitis, andother conditions during infusion therapy. The control unit 900 performsoperations including measurement control, information processing, datastorage, and display of results. In some applications, the control unit900 may process data in real time or may collect data for subsequentanalysis.

[0167] In the illustrative example, the control unit 900 is housed in acase 1010 a suitable size for attachment to a patient's arm or leg,taped to an alternative portion of the body, or mounted onto an IV pole.The control unit 900 has a visual display 1012 to facilitate viewing bythe patient, health care provider, or others. The visual display 1012,for example a liquid crystal display, a computer screen, a personaldigital assistant (PDA) screen, a pager visual screen, cellular phonedisplay screens, or any other suitable display. The display 1012 candisplay various information including results and indications derivedfrom sensor information, alert notifications, current time and date aswell as time and date of pertinent events. The visual display 1012 canalso display time and date of past and upcoming infusions. The controlunit 900 may have an alarm that generates a notification signal such asan audio alarm, vibration, illumination signal, or other suitable typesof enunciator.

[0168] The control unit 900 stores and compares various types ofinformation to diagnose tissue condition. One or more of various typesof data can be stored, compared, and analyzed, for example includingcurrent data, reference data, baseline data, information trends, presetparameters, automatic comparison results, patient condition informationfor disease condition adjustments, environment information, cannulaposition and motion information, and infusion flow information.

[0169] In some embodiments, the case 1010 may include an inlet fluidconductor 1014 that is capable of connecting a proximal conduit 1016 toan intravenous fluid source 1018 such as a syringe, a pump, or an IVbag. An outlet fluid conductor 1020 connects a distal conduit 1022 to anintravenous discharge device 1024 that discharges fluid into a patient'sblood vessel.

[0170] Information stored in the control unit 900 may be visuallypresented on the visual display 1012 and/or communicated to a remotereceiving device 930 via a transmitter/receiver 934 for storage oranalysis. The transmitter/receiver 934 may be either a hardwire orwireless device.

[0171] Referring to FIG. 11, a flow chart depicts an example of atechnique for detecting a harmful tissue condition, for exampleintravascular infiltration, intravascular extravasation or tissuenecrosis, during infusion. In an initialization operation 1110 prior toinfusion initiation, a film barrier dressing with sensors is affixed tothe skin 1112 to one or more sites including the proposed vascularinsertion site of a needle or cannula into the vascular pathway.Interconnect lines are connected from the film barrier dressing sensorsto a control unit. Additional sensor dressing may be applied to otherlocations at risk for complications.

[0172] The sensors are capable of interrogating the tissue and receivingtissue condition signals using one or more sensing technologies.Suitable sensing technologies may include bio-potential, bio-impedance,photonics, optical sensors, acoustic, ultrasound, and others. In oneexample, a photonics detector has an infrared generator and a photonicsdetector. The infrared generator produces a beam of light that scans thesurface skin and subcutaneous tissue during monitoring, causing thephotonics detector to generate a pulse signal that can be analyzed todetermine tissue condition.

[0173] The infusion system begins monitoring prior to insertion toobtain baseline pre-infusion information 1114 at the plurality of sitesin a start mode of operation. During the start mode, the control unitrecords the baseline data and generates a normal characterization oftissue. For example, an extravasation analysis may begin by determininga pre-injection baseline measurement of the tissue impedance bycollecting preliminary data prior to injection.

[0174] In an illustrative example, monitoring beings by injecting acurrent across the monitored tissue 1116, measuring a parameter 1118such as impedance during application of the current, and storing theparameter 1120 in a memory. In one example, a constant sinusoidalalternating current is applied to the first electrode pair at a currentof approximately 200 uA and frequency of about 20 kHz and the voltagepotential at the second electrode pair is measured. Other suitablecurrents and frequencies may be used. For example, Electrical ImpedanceTomography imaging typically uses frequencies above 1 kHz and less than100 kHz, although some applications may utilize frequencies up to 10 mHzand above. A system with capability to operate in a frequency rangebetween 10 kHz and 10 MHz is highly flexible.

[0175] An increase or decrease in electrical conductance and capacitancemay occur resulting from changes in the tissue.

[0176] Continuous calculations of tissue impedance are made during theinjection therapy. The film barrier dressing remains affixed to thepatient during monitoring. Monitoring continues over time 1121 and themeasured and stored parameter is compared to past values 1122 includingthe stored baseline values. For multiple-site sensors, the infusionsystem compiles an impedance map 1124 that depicts impedancemeasurements over a two-dimensional or three-dimensional space.

[0177] A processor accesses the stored time and space impedance samplesand performs a thresholding and pattern recognition operation 1126. Thefilm barrier dressing remains affixed to the patient and monitoringcontinues over time during infusion. The infusion system determines thepresence or absence of infiltration and extravasation 1128 based on thethreshold analysis and pattern recognition operation, and conveysresults to a display screen 1130 for visual notification of a caretaker.In an example of a thresholding and pattern recognition operation 1126,if data such as photonics, optical, and impedance are acquired, theanalysis may include operations of: (1) sensing infrared information andbio-impedance information, (2) comparing the information to presetthresholds, and (3) forming an information map indicative of thephysical or geometric contours of the acquired parameter. Various typesof information maps include photonics infrared reflection maps, opticalspectrographics maps, and bio-impedance maps.

[0178] In one example, extravasation is indicated if the impedancechanges with a substantially consistent slope of ±0.5 Ω/s or more duringinfusion at a rate of at least 1000 cc over 24 hours or an intermittentinfusion of over 100 cc in one hour.

[0179] In an example, tissue impedance is considered to be affected byextravasation because ionic contrast media has lower impedance thantissue. For ionic contrast media extravasation, measured impedance isless than the measured tissue impedance prior to extravasation. Anon-ionic contrast media has higher impedance than tissue and causesincreased impedance during an extravasation.

[0180] The infusion system can send an alert signal 1132, such as anaudio annunciation or alarm, when a harmful condition occurs.Accordingly, the infusion system functions as a medical surveillancesystem to determine the condition of tissue as a patient receives aninfusion to allow a caretaker to intervene early, reducing complicationsassociated with intravascular infusion. The alert notification may alsoinclude transmission of the alert notification and analysis informationin-the form of a status report that are sent to a remote device, forexample by wireless transmission of patient status information, forexample to a computer, a pager, personal digital assistant (PDA),internet interface, or land line.

[0181] In another example, during the act of obtaining baselinepre-infusion information 1114, the baseline impedance represents theimpedance measured at the zone of injection prior to starting injection.The pattern recognition operation 1126 determines the occurrence ofextravasation by two characteristics, that the impedance varies from thebaseline by more than a first predetermined threshold and that the rateof change of impedance, called the slope, is consistently larger than asecond predetermined threshold.

[0182] To reduce false-positive indications of extravasation, apredetermined number of measurements are to deviate past the firstpredetermined threshold from the baseline, and the rate of change of theimpedance measurements is to exceed a certain absolute value and do soconsistently.

[0183] In another example, the thresholding and pattern recognitionoperation 1126 compiles individual historical and real time informationon the status of a patient. Analyzed data includes continuouslymonitored data samples from one or more cross-sectional tissue areas.The time history of samples is analyzed to detect changes from referenceinformation and baseline values, and monitor data trends. The analysismay include adjustments for known disease conditions, for example topredict likely trends and determine results outside the prediction.Rapid value changes may be indicative of physical movement or disruptionof the needle or catheter at the insertion site.

[0184] The infusion system 100 can alternatively be used to monitor forphysiological conditions relating to tissue grafting of artificial ornatural tissue to detect the presence of tissue necrosis that mayindicate rejection of new tissue.

[0185] In other applications the infusion system 100 can be used formonitoring, analysis, detection of complications, and generation ofcomplication alarms in hydration monitoring, wound closure,pharmacokinetic monitoring, monitoring and mapping of tissue in multipleablation freezing applications including radio frequency, laser, andcryosurgery applications, and others. For example, an infusion system100 that monitors overhydration and hypersensitivity to infusions andinfections may include temperature monitoring and heart electricalsignal monitoring that can detect circulatory overload. Infections cancause elevation in temperature and circulatory overload causes the heartrate to increase.

[0186] In another example, conductivity maps may be used to determine atemperature distribution. Temperature mapping can be used for manyapplications including object recognition in noninvasive surgery while asurgeon cuts or ablates tissue by cryotherapy, knife, laser, radiofrequency, or other cutting and ablating techniques. Mapping can be usedto visualize cancer and reduce cutting of healthy tissue. Temperaturemapping can be used for various applications including cancer treatmentin liver and other organ tissues, breast biopsy, and the like.Temperature mapping using sensors in the frame of a dressing with aninterior transparent window allows visualization in combination withtemperature mapping. Temperature mapping can also be used in combinationwith ultrasound imaging.

[0187] Following generation of the alarm, a caretaker typically visuallyexamines the site 1134 through the transparent dressing to detect IVcomplications such as dislodgement or movement of the catheter or needlefrom the original placement position. Complications are evidenced byvisible blood, fluid beneath the dressing, or movement of the cannula orneedle. Other visual cues of complication include tissue redness,swelling, tightness, and vein inflammation.

[0188] The caretaker can palpate the patient 1136 to detect tendernessor patient discomfort, swelling, or increase in skin temperature.Swelling may increase since IV infusions have an osmotic effect and drawwater into the tissue.

[0189] The automatic alarm is a computer-aided diagnostic that enablesthe caretaker to assess patient condition to determine whether tocontinue or terminate the IV infusion. The automatic alarm gives acapacity for early detection of complications before symptoms arevisible or before quickly arising complications reach critical levels.Upon detection of IV complications, the caretaker can terminate theinfusion 1140.

[0190] Referring to FIG. 12, a schematic circuit diagram shows animpedance model of tissue that is useful for describing conductivityreconstruction in tissue. Techniques for determining and mappingconductivity distribution in tissue supply useful information ofanatomical and physiological status in various medical applications.Electrical Impedance Tomography (EIT) techniques are highly suitable foranalyzing conductivity distribution. Electrical characteristics oftissue include resistive elements and capacitive elements. EITtechniques involve passing a low frequency current through the body tomonitor various anatomical and physiological characteristics. The systemcan interrogate at multiple frequencies to map impedance. Analyticaltechniques involve forward and inverse solutions to boundary valueanalysis to tissue characteristics.

[0191] Multiple electrodes are placed in contact with tissue and aconstant current is applied to the tissue across a subset of theelectrodes, and impedance or resistance is measured at other electrodes.For example, tissue can be excited by an electric current and impedanceis determined by measuring the electric potential generated by thecurrent. In other examples, a voltage can be generated and a currentmeasured. Current interrogation and voltage measurement typicallyproduces a more accurate impedance measurement and has a lower outputnoise and better sensitivity. Conductivity distribution can be mapped intwo dimensions or three dimensions. The illustrative technique solvesthe inverse problem in full three dimensions. Two dimensional images areobtained by slicing the three dimensional images.

[0192] Referring to FIG. 13, a schematic block diagram shows aneight-electrode configuration for a tissue impedance measurement. Themultiple electrodes can be connected to one impedance analysis circuit(not shown) via a multiplexer (not shown). Four electrodes 1310 are usedto apply current to the tissue 1302, and four electrodes 1314 are usedto sense body electrical activity that results from application of thecurrent. The differential voltage evoked by the applied current ismeasured at a differential amplifier 1320. In an illustrativeembodiment, the electrodes can be spaced equidistant about a circle,square, or any other suitable cross-section. The illustrative analysistechnique is highly flexible allows three-dimensional imaging when theelectrodes are formed in any configuration. In other embodiments, theelectrodes need not be equidistant. Any number of electrodes may beused. For example, a suitable sensor can use 32 or any other number ofelectrodes. Generally, the electrodes are spaced with a sufficient gapfor distinguishing electrical signals.

[0193] The illustrative imaging technique is very flexible and allowsinterrogation using any current pattern, using the complete electrodesmodel, rather than a point electrode model.

[0194] In one embodiment, the tomography method constructs a simpleimage with 15 pixels. Other image configurations are suitable.

[0195] Referring to FIG. 14, an Electrical Impedance Tomography (EIT)block diagram shows a two-dimensional configuration of tissue at objectB mapped by a conductivity measurement device. A mathematical model ofthe forward problem for conductivity is depicted in equations (3-6) asfollows:

∇·[δ′(P)·∇U′(P)]=0 at object B   (3)

δ′(P)(∂U′(P)/∂η)=J P∈S   (4)

∫_(S) U′(P)ds=0   (5)

[0196] where U(P) is voltage and δ(P) is specific admittance of B, inwhich:

δ′(P)=δ(P)′jωε(P)   (6)

[0197] S is surface boundary of B.

[0198] A boundary value problem is defined in which conductivitydistribution σ is real and positive throughout the field, ν is apotential distribution, η is an outward normal, J is applied flux, Ω isa domain of interest, and ∂Ω designates the domain boundry. The boundaryvalue problem can be solved using a Finite Element Method (FEM) thatproduces a linear system of equations with the form shown in equation(7):

Yν=c   (7)

[0199] where Y is a global stiffness matrix, ν is a vector representingthe potential distribution at node of the elements and c is effectiveapplied current at the nodes.

[0200] Referring to FIG. 15, a schematic pictorial diagram shows aFinite Element Method (FEM) mesh. In the forward problem, the potentialdistribution of a domain is calculated given a known conductivitydistribution and a known current source for boundary conditions. In theinverse problem analysis, a voltage is measured and the currentinjection pattern is known. From the known voltage and current injectionpattern, the conductivity pattern is sought that produces the measuredvoltages. A difficulty is that in EIT, boundary potentials vary at anypoint in the conductivity distribution in a nonlinear manner.

[0201] The illustrative Electrical Impedance Tomography technique uses aregularized Newton-Raphson method to optimize the ill-posed inverseproblem for imaging and mapping. The optimization problem attempts tofind a best conductivity distribution that fits measured data. Imagereconstruction uses nr to optimize the ill-posed inverse problem forimaging and mapping. The optimization problem attempts to find a bestconductivity distribution that fits measured data. Image reconstructionuses Newton-Raphson regularization to stabilize the numerical solutionof the ill-posed inverse problem. Image reconstruction based on theNewton-Raphson method uses an efficient method for Jacobian matrixcomputation. Tikhonov regularization is used in the Newton-Raphsonmethod to stabilize image reconstruction.

[0202] The inverse problem in three dimensional Electrical ImpedanceTomography imaging is ill-posed and nonlinear. Several methods can beused for image reconstruction of both low and high contrastconductivity. EIT imaging can be cased on the Born approximation,particularly for low contrast conductivity reconstruction where littleadvantage is gained in recalculation of the Jacobian.

[0203] Sensitivity Analysis using the Jacobian is depicted according toFIG. 16. When a conductivity distribution changes from σ to σ+Δσ, thetransfer impedance change ΔZ for pairs of current and voltage electrodesA,B and C,D, respectively are shown in equation (8):

ΔZ=−∫ _(Ω)Δσ(∇u(σ)/I _(u))·(∇ν(σ+Δσ)/I _(ν))dΩ  (8)

[0204] where u is the potential distribution over the field when thecurrent I_(u) is applied at electrodes A,B with a conductivity of σ.Similarly, ν is potential over the field when the current I_(ν) isapplied at electrodes C,D with a conductivity of σ+Δσ. Equation (8)assists solution of the inverse problem by allowing estimation of aconductivity σ and calculation of u given current I_(u) in the forwardanalysis. The difference between the calculated potential distribution uand the measured potential distribution ν gives value ΔZ. Using valueΔZ, conductivity distribution Δσ can be solved. The sensitivity methodis very general and allows determination of sensitivity directly andwith any distribution of conductivity. Other less suitable methods onlyallow calculation of sensitivity in a homogenous conductivity area.

[0205] A Newton-Raphson technique can be used to minimize a function φwith respect to σ defined according to equation (9):

φ=½(η−V)^(T)(η−V)   (9)

[0206] Minimization of φ is the Gauss-Newton iteration shown in equation(10):

Δσ_(k)=−[η′(σ_(k))^(T)η′(σ_(k))]⁻¹η′(σ_(k))^(T)[η(σ_(k))−V]  (10)

[0207] The φ iteration is ill-conditioned and further exacerbated bynoisy data.

[0208] A simple iterative scheme can be used to combine the forwardproblem and the inverse problem. First, estimate σ_(k) and consequentlycalculated η. Second, compare the calculated η and the measured V.Third, adjust σ_(k) and calculate a new η. Fourth, iterate until ∥V−η∥reaches a specified criterion.

[0209] In a regularized Newton-Raphson method depicted in FIG. 17, aninitial conductivity distribution is given 1710 which is presumed to bezero. The forward problem is solved 1712 and predicted voltages arecompared with calculated voltages from the finite element model.Conductivity is updated using a regularized inverse of the Jacobian. Theprocess is repeated 1714 until predicted voltages from the finiteelement method agree with measured voltages. The update formula is shownin equation (11):

σ_(n+1)=σ_(n)+(J _(n) *J _(n) +R)⁻¹ J _(n)*(V _(measured) −F(σ_(n)))  (11)

[0210] J_(n) is the Jacobian calculated 1716 with the conductivityσ_(n). V_(measured) is the vector of voltage measurements and theforward solution F(σ_(n)) is the predicted voltage from the finiteelement model with conductivity σ_(n). The matrix R is a regularizationmatrix that penalized extreme changes in conductivity, correctinginstability in the reconstruction at the expense of producingartificially smooth images. To solve the full matrix inverse problem1718, information obtained from the forward measurement is used. Theinverse problem calculates a conductivity distribution σ_(n) given a setof current injection patterns I and a set of measured voltages V. Theforward problem 1720 calculates voltages η given a current injectionpattern I and a conductivity distribution σ 1722.

[0211] While the invention has been described with reference to variousembodiments, it will be understood that these embodiments areillustrative and that the scope of the invention is not limited to them.Many variations, modifications, additions and improvements of theembodiments described are possible. For example, those skilled in theart will readily implement the steps necessary to provide the structuresand methods disclosed herein, and will understand that the processparameters, materials, and dimensions are given by way of example onlyand can be varied to achieve the desired structure as well asmodifications which are within the scope of the invention. Variationsand modifications of the embodiments disclosed herein may be made basedon the description set forth herein, without departing from the scopeand spirit of the invention as set forth in the following claims.

[0212] In the claims, unless otherwise indicated the article “a” is torefer to “one or more than one.”

What is claimed is:
 1. A tissue monitoring apparatus comprising: a filmbarrier dressing comprising a flexible membrane integrating one or moresensor elements and an adhesive layer capable of coupling to a patient'sskin; and a control unit capable of coupling to the one or more sensorelements in the film barrier dressing, the control unit capable ofcontrolling the sensor elements, sensing one or more parametersindicative of tissue condition in three-dimensional space, and executinga three-dimensional pattern recognition operation on the one or moresensed parameters to determine a tissue condition.
 2. A tissuemonitoring apparatus according to claim 1 wherein: the flexible membraneis at least partially transparent so that a patient's tissue underlyingthe film barrier dressing can be visually inspected.
 3. A tissuemonitoring apparatus according to claim 1 wherein: the film barrierdressing is a breathable barrier film that protects against infectionand functions as a structural member that is capable of securing anintravenous catheter.
 4. A tissue monitoring apparatus according toclaim 1 further comprising: a bio-impedance sensor, the control unitcapable of executing a pattern recognition operation in one or moredimensions on the impedance signals to determine the tissue condition.5. A tissue monitoring apparatus according to claim 1 furthercomprising: a bio-impedance sensor and an optical sensor, the controlunit capable of executing a pattern recognition operation in one or moredimensions on the impedance signals and the optical signals to determinethe tissue condition.
 6. A tissue monitoring apparatus according toclaim 1 further comprising: a bio-impedance sensor including a pluralityof sensor elements configured to acquire impedance signals inthree-dimensional space; and a tomography processor executable in thecontrol unit and capable of executing a three-dimensional tomographyoperation on the impedance signals.
 7. A tissue monitoring apparatusaccording to claim 1 further comprising: a bio-impedance sensorincluding a plurality of sensor elements configured to acquire impedancesignals in three-dimensional space; and a tomography processorexecutable in the control unit and capable of executing a objectrecognition operation on the impedance signals.
 8. A tissue monitoringapparatus according to claim 1 further comprising: a bio-impedancesensor including a plurality of sensor elements configured to acquireimpedance signals; and a fast reconstruction technique tomographicprocessor executable in the control unit and capable of mapping theimpedance signals in space.
 9. A tissue monitoring apparatus accordingto claim 1 further comprising: an optical sensor comprising a pluralityof sensor elements configured to acquire optical signals inthree-dimensional space, the sensor elements comprising an infraredgenerator and a photonics detector; and a tomography processorexecutable in the control unit and capable of executing athree-dimensional tomography operation on the optical signals.
 10. Atissue monitoring apparatus according to claim 1 further comprising: anoptical sensor including a plurality of sensor elements configured toacquire optical signals; and a tomography processor executable in thecontrol unit and capable of mapping the optical signals in space.
 11. Atissue monitoring apparatus according to claim 1 further comprising: abiosensor capable analytic chemistry measurements of electrolyte levelsfor detecting electrolyte abnormalities.
 12. A tissue monitoringapparatus according to claim 1 further comprising: a memory capable ofstoring sensor information including historical information and currentinformation acquired in real time; and an analysis process capable ofcomparing information in one or more categories of a group includingcurrent data, reference data, baseline data, information trends, presetparameters, automatic comparison results, patient condition informationfor disease condition adjustments, environment information, cannulaposition and motion information, and infusion flow information.
 13. Atissue monitoring apparatus according to claim 1 further comprising: asensor electrode array including equally-spaced electrodes in ageometrical configuration; and a multiple-frequency analysis processexecutable in the control unit that analyzes data from the multiplereference points to generate a spectrographic composite for monitoringover time.
 14. A tissue monitoring apparatus according to claim 1further comprising: an analysis process executable in the control unitthat analyzes sensor information to detect one or more of infiltration,extravasation, blood clots, and phlebitis in an intravascular infusionoperation.
 15. A tissue monitoring apparatus according to claim 1further comprising: an analysis process executable in the control unitthat analyzes sensor information to detect tissue necrosis and rejectionin a tissue graft of artificial or natural tissue.
 16. A tissuemonitoring apparatus according to claim 1 further comprising: ananalysis process executable in the control unit that analyzes sensorinformation to monitor tissue hydration.
 17. A tissue monitoringapparatus according to claim 1 further comprising: an analysis processexecutable in the control unit that analyzes sensor information tomonitor wound closure.
 18. A tissue monitoring apparatus according toclaim 1 further comprising: an analysis process executable in thecontrol unit that analyzes sensor information for pharmacokineticmonitoring.
 19. A tissue monitoring apparatus according to claim 1further comprising: an analysis process executable in the control unitthat analyzes sensor information to detect tissue necrosis and rejectionin a tissue graft of artificial or natural tissue.
 20. A tissuemonitoring apparatus according to claim 1 further comprising: atransmitter in the control unit capable of sending diagnosticinformation to a remote receiver for remote surveillance of tissuemeasurements and characteristics.
 21. A tissue monitoring apparatusaccording to claim 1 further comprising: a wireless transmitter in thecontrol unit capable of sending diagnostic information to one or moreremote receivers for remote surveillance of tissue measurements andcharacteristics.
 22. A tissue monitoring apparatus according to claim 1further comprising: a wireless transmitter in the control unit capableof sending diagnostic information to one or more remote receiversincluding one or more of personal computers, personal digitalassistants, pagers, remote visual display screens, and cellulartelephones.
 23. A tissue monitoring apparatus according to claim 1further comprising: a transmitter in the control unit capable of sendingcontrol information to an infusion pump controller for controllingintravascular infusion.
 24. A tissue monitoring apparatus according toclaim 1 further comprising: an analysis process executable in thecontrol unit that analyzes sensor information for monitoring and mappingtissue in multiple ablation freezing applications including radiofrequency, laser, and cryosurgery applications.
 25. A tissue monitoringapparatus comprising: means for flexibly covering and protecting apatient's skin; means integrated into the covering and protecting meansfor sensing one or more biological parameters; means for acquiringthree-dimensional biological information from the sensing means; andmeans for analyzing patterns in the three-dimensional biologicalinformation; and means for determining a patient tissue condition basedon the analyzed patterns.
 26. A tissue monitoring apparatus according toclaim 25 wherein: the covering and protecting means further comprises atransparent window enabling visualization of the patient's tissue andmeans for securing an intravenous catheter.
 27. A tissue monitoringapparatus according to claim 25 further comprising: means for measuringbio-impedance of the patient's tissue; means for interrogating thepatient's tissue using optical sensing; and means for analyzing thepatient's tissue using pattern recognition of the bio-impedancemeasurements and optical sensing to determine the tissue condition. 28.A tissue monitoring apparatus according to claim 25 further comprising:means for measuring bio-impedance of the patient's tissue; and means foranalyzing the patient's tissue using pattern recognition of thebio-impedance measurements to determine the tissue condition.
 29. Atissue monitoring apparatus according to claim 25 further comprising:means for measuring bio-impedance of the patient's tissue; means forinterrogating the patient's tissue using optical sensing; means foranalyzing the patient's tissue using a three-dimensional tomographyoperation on the optical signals and the bio-impedance measurements todetermine the tissue condition.
 30. A tissue monitoring apparatusaccording to claim 25 further comprising: means for storing sensorinformation including historical information and current informationacquired in real time; and means for comparing information in one ormore categories of a group including current data, reference data,baseline data, information trends, preset parameters, automaticcomparison results, patient condition information for disease conditionadjustments, environment information, cannula position and motioninformation, and infusion flow information.
 31. A tissue monitoringapparatus according to claim 25 further comprising: means for analyzingsensor information to detect infiltration and extravasation in anintravascular infusion operation.
 32. A tissue monitoring apparatusaccording to claim 25 further comprising: means for analyzing sensorinformation to detect tissue necrosis and rejection in a tissue graft ofartificial or natural tissue.
 33. A tissue monitoring apparatusaccording to claim 25 further comprising: means for sending diagnosticinformation to a remote receiver for remote surveillance of tissuemeasurements and characteristics.
 34. A tissue monitoring apparatusaccording to claim 25 further comprising: means for sending diagnosticinformation to one or more remote receivers including one or more ofpersonal computers, personal digital assistants, pagers, remote visualdisplay screens, and cellular telephones for remote surveillance oftissue measurements and characteristics.
 35. A method of monitoring apatient tissue condition comprising: attaching a film barrier dressingto a patient skin surface, the film barrier dressing comprising aflexible membrane integrating one or more sensor elements and anadhesive layer capable of coupling to the patient's skin; communicatinginformation from the one or more sensor elements to a control unit;controlling the sensor elements to sense one or more parametersindicative of tissue condition in three-dimensional space; in a startmode, acquiring information from the one or more sensor elements andrecording baseline information; commencing a intravascular infusionoperation; in a test mode, acquiring information from the one or moresensor elements and recording test information; and comparing thebaseline information and the test information in three-dimensions usingpattern recognition using the one or more sensed parameters to determinea tissue condition.
 36. A method according to claim 35 furthercomprising: storing sensor information including historical informationand current information acquired in real time; and comparing informationin one or more categories of a group including current data, referencedata, baseline data, information trends, preset parameters, automaticcomparison results, patient condition information for disease conditionadjustments, environment information, cannula position and motioninformation, and infusion flow information.
 37. A method according toclaim 35 further comprising: sending diagnostic information to a remotereceiver for remote surveillance of tissue measurements andcharacteristics.
 38. A method according to claim 35 further comprising:sending diagnostic information to one or more remote receivers includingone or more of personal computers, personal digital assistants, pagers,remote visual display screens, and cellular telephones for remotesurveillance of tissue measurements and characteristics.